Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Principles Of Disease And Treatment > Genetics And Cell Biology > Flashcards

Genetics And Cell Biology Flashcards

1
Q

Describe features of prokaryotes and eukaryotes

A

Prokaryotes:

  • 2 groups or domains: archaea and bacteria
  • no organelles
  • no nucleus
  • DNA with circular genome
  • most diverse kind of cells

Eukaryotes:

  • have discrete organelles
  • have a nucleus (membrane bound structure containing DNA)
  • have mitochondria
  • have others such as Golgi and endoplasmic reticulum and lysosomes etc
  • different types of cells for different functions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Draw a labelled diagram of a cell membrane

A

See lecture 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Label a diagram of a mammalian cell

A

See lecture 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Define cellular homeostasis

A

the property of a system, especially a living organism, to regulate its internal environment so as to maintain a stable, constant condition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Why do cells maintain homeostasis

A

Key things (like temperature, pH, osmolality, ionic concentrations etc) have to be kept in narrow tolerances

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How is homeostasis maintained

A
  • alter properties
  • programmed cell death (apoptosis) necessary in multicellular animals
  • infected or unhealthy cells “commit suicide” (altruism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How many bonds are between adenine and thymine

A

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How many bonds are between cytosine and guanine

A

3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe how covalent bonds and ionic bonds allow for stable arrangement of atoms

A

Both form strong bonds
Covalent bonds: between 2 non-metals and similar electronegativity
Ionic bonds: between metal and non- metals with different electronegativity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are homopolymers

A

Polymers that are made of many copies of the same molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are heteropolymers

A

Polymers created from different assemblies of different building blocks

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the four main polymers found in cells? Give a brief description of each

A
  1. Polysaccharides: polymers of sugars - typically homopolymers
  2. Fats/lipids: polymers of carbons with other groups attached
  3. Nucleic acids: polymers of nucleotide bases in specific sequences ( heteropolymers)
  4. Proteins: polymers of 20 different amino acids in specific sequences (heteropolymers)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the key components of sugars

A
  • simplest are monosaccharides- (CH2O)n
  • can be drawn as chains or rings - alpha and beta links (hydroxyl group on the carbon that carries aldehyde or ketone can rapidly change from one position to the other)
  • disaccharides are simple polysaccharides (formed by glycosidic bonds)
  • large linear and branched molecules can be made from simple repeating units - short chains are called oligosaccharides and long chains are called polysaccharides eg cellulose and glycogen
  • glycogen is the stable storage form of glucose in the body
  • cell surface glycoproteins are proteins with sugar on top
  • one sugar group determines the difference between the ABO blood groups
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do you form sucrose, maltose and lactose

A 
Sucrose = glucose + fructose
Maltose = glucose + glucose
Lactose = glucose + galactose
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe the key properties of fatty acids

A
  • components of cell membranes
  • stored in the cytoplasm as triacylglcerol - can be released from it when a cell needs energy (done via acetyl CoA)
  • saturated fats have no double bonds (solids and not very reactive)
  • unsaturated fats have double bonds (don’t pack well and are quite reactive + they are oils)
  • phospholipids aggregate to form cell membranes
  • proteins are embedded in the plasma membrane lipid bilayer (can have many key roles eg transporters, anchors, receptors, enzymes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does amphipathic mean

A

Both hydrophilic and hydrophobic regions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe the key properties of nucleic acids

A
  • form nucleotides
  • basis of DNA and chromosomes
  • nucleotides perform a variety of functions in cells
    1. Carry chemical energy in their easily hydrolysed phosphoanhydride bonds
    2. Combine with other groups to form coenzymes
    3. Used as signalling molecules in the cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Draw the general formula for an amino acid

A

See lecture 2 slide 36

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Give two examples of diseases caused by protein assembly going wrong. Briefly describe each

A
  1. Cystic fibrosis: mutations in Cl- ion channel cause a misfolding of the channel that prevents correct Cl- transport
  2. Alzheimer’s disease: misfolding and aggregation of a protein called b-amyloid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Sketch a labelled diagram of a double stranded DNA molecule. To which end are new bases added

A

See lecture 3 slide 7

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the sugar in RNA and what is it in DNA

A 
RNA = ribose
DNA = deoxyribose
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What group the bases in DNA and RNA into purines and pyrimidines

A

Purines: Adenine and Guanine
Pyrimidines: cytosine, thymine and uracil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Draw a simple labelled diagram of DNA replication at the replication fork

A

See lecture 3 slide 13

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is released when a base is added during DNA synthesis

A

Pyrophosphate

P2O7^4-

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What enzyme catalyses DNA replication. Describe in one sentence what it does

A

DNA polymerase
It catalyses the addition of nucleotides to the growing end (3’ OH) of a new DNA molecule, it stays attached to the DNA and adds new bases stepwise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

How is DNA made in the “lagging strand” where the direction is 5’ to 3’

A
  • short strands called Okazaki fragments are made in the 5’ to 3’ direction
  • these strands are made in small pieces discontinuously
  • DNA ligand joins them together via “backstitching”
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is the main enzyme involved in transcription

A

RNA polymerase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Describe alternative splicing

A

Some RNAs use different combinations of exons to form different proteins
Different tissues can express different versions of the same RNA generated by alternative splicing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What are the start and end codons

A

Start - Met (AUG)

End - UGA, UAA, UAG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Give two examples of congenital diseases caused by genetics

A

Down’s syndrome

Cystic fibrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What is the definition of a diagnosis of a genetic disease

A

Testing of patient, following indicative clinical findings, to confirm genetic diagnosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Definition of newborn screening

A

Testing of newborn to identify conditions that require immediate initiation of treatment to prevent death or disability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Definition of carrier tests

A

Testing to identify an asymptomatic adult who is a carrier for autosomal-recessive or X-linked recessive conditions. Testing is usually initiated in the basis of family history or because the genetic condition is common among individuals of the patients ethnicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Definition of prenatal tests

A

Testing to identify a foetus with a genetic condition. Testing is usually initiated on the basis of maternal factors or family history that indicate increased risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Definition for tests for adult-onset genetic conditions

A

Testing of asymptomatic young adults to identify a genetic condition that will occur later in life, such as Huntington’s disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Why is it particularly important that diagnostic and susceptibility tests have no (very low) false negative rate and a low false positive rate

A

No false negative rate: tell ppl they don’t have it - but they actually do - means you can end up missing ppl
Low false positive rate: identify that they have it but they don’t actually - must always follow up to confirm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Name 3 things along with examples of each that can be tested for in a diagnostic or susceptibility test

A

Chromosomes - trisomy 21; Down syndrome
Specific mutations - cystic fibrosis
Specific gene - polycystic kidney disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Give 5 examples of things NIPT is good to detect

A 
Down syndrome
Edwards syndrome
Palau syndrome
Turner syndrome 
Fetal sex determination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What population (prenatal) screening occurs in the UK

A

Downs and Edwards and Pataus syndrome combined test
Sickle cell disease
Thalassaemia

Newborn and infant physical examination (NIPE) screens newborns within 72 hours of birth

General foetal screening by careful ultrasound examination for structural abnormalities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Give an example of a disease identified through newborn screening

A

Sickle cell disease
Cystic fibrosis
Congenital hypothyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

How is transcription regulated

A 
DNA packaged around histone proteins: Chromatin
Histone modification (acetylation) regulates access to the DNA
Histone acetylation increases transcription
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What do transcription factors do

A

Create conditions for transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What do microRNA do and how do they do it

A

miRNAs regulate mRNAs
Work as part of RISC (RNA-Induced Silencing Complex)
miRNAs ‘tell’ RISC which mRNAs to target
miRNAs bind to mRNA - specific RNA sequence - complimentary

They do it by:
Causing them to be degraded
Prevent them from being translated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Give two clinical examples of how circulating microRNAs can be used as biomarkers

A

Clinical applications to date
Cardiovascular disease

Cancer

  • Clinical test to differentiate between chronic pancreatitis and pancreatic cancer (Asuragen)
  • Cancer Origin Test™ (Rosetta)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

How can PCR be used in diagnostics

A

Virology (multiply virus to check if it’s there)
Detection of bacteria
Forensics and paternity kits
All genetic tests

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

4 applications of NGS

A

Mutation detection
Pharmacogenetics
Gene expression
Microbiology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Draw and label a diagram of a chromosome

A

See lecture 5

Slide 12

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What is a nucleosome

A

DNA wrapped around 8 his tone proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is chromatin

A

Network of DNA & proteins that make up chromosomes during interphase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is heterochromatin

A

Highly condensed and genetically inactive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is euchromatin

A

Lighter staining, relatively open structure where genes may be accessed and are active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Draw the four classifications of chromosomes

A

See lecture 5

Slide 15

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Describe mitosis

A

See lecture 5

Slide 18

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Describe meiosis

A

See lecture 5

Slide 19

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

what does ploidy and aneuploidy mean

A

Ploidy: wrong number of complete chr sets
Aneuploidy: specific additional or missing chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Which bases are the purines and which bases are the pyrimidines

A

Purines are adenine and guanine

Pyrimidines are cytosine and thymine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

list the different types of DNA mutation

A 
Point mutations
Insertions and deletions
Gene deletions
Translocations
Complex chromosomal 
	rearrangements
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

what are transitions and transversions in relation to DNA bases

A

Transitions are interchanges of two-ring purines (A G) or of one-ring pyrimidines (C T): they therefore involve bases of similar shape.
Transversions are interchanges of purine for pyrimidine bases, which therefore involve exchange of one-ring and two-ring structures

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

What are the three types of point mutation? Describe them

A

Silent - no change in protein
Nonsense - incomplete protein - mutation causes a stop codon
Missense - faulty protein - codon changes which protein is made

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

How can the location of a mutation change its effect

A

In the coding sequence
- change the protein or stop translation

In the promoter or non-coding regions
- Alter expression levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Describe triplet repeat disorders and list 3 disease examples

A

Triplet repeat disorder occur due to an increase in the number of specific triplet repeats. Conditions tend to get worse through generations (anticipation) as the number of repeats increases due to errors during replication. The effects depend upon the location of the repeat, whether in coding regions (eg polyQ conditions) or in non-coding regions.
Examples include Fragile X Syndrome, Myotonic Dystrophy, Huntington Disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What type of mutation causes Cystic fibrosis and what kind of inheritance is it

A

Deletion of the codon for the 508th amino acid (phenylalanine, F) in the cystic fibrosis conductance regulator (CFTR) gene

Autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What type of mutation causes sickle cell disease and what kind of inheritance is it

A

Single nucleotide missense mutation

Autosomal recessive

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What kind of mutation causes Beta Thalassemia and describe its inheritance pattern

A

Lots of mutations - mostly point mutations
Severity depends on mutation
Heterozygous state - mild
Homozygous state - moderate or severe

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What type of mutations cause haemophilia and what is it’s pattern of inheritance

A

X linked recessive

Simple and complicated mutations:
Deletions, point and rearrangements

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Compare the influence of different gene mutations upon the pattern of inheritance of a disease

A

Gain of function often dominant inheritance, eg Huntingdon’s disease
Loss of function usually recessive, eg thalassaemia
Loss of function of gene on X chromosome X-linked recessive, eg haemophilia
Fragile X mental retardation causes loss of function but this has a dominant effect (ie males with one mutated copy are affected) – this is X-linked dominant inheritance.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Give 4 treatment strategies for genetic diseases. Give examples for each

A
  • Gene therapy, e.g. vector-based (eg adenovirus),CRISPR-Cas9, CAR T (Acute Lymphoblastic Leukaemia & Diffuse Large B-Cell Lymphoma)
  • Block downstream cellular pathway (eg Sirolimus in Tuberous Sclerosis)
  • Enzyme replacement, e.g. Alpha-Galactosidase in Fabry Disease
  • Substrate reduction, eg some enzyme deficiencies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

What does aneuploidy mean

A

Abnormal number of chromosomes within a cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What does mosaicism mean

A

Different populations of cells with different numbers of chromosomes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

How does FISH work

A

Uses specific dye-labelled DNA sequence to hybridise to chromosomal region of interest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q 
A patient shows these symptoms, what is the syndrome?
Cardiac abnormalities
Thymic hypoplasia; T cell abnormalities
Hypocalcaemia
Cleft palate
Abnormal ears, micrognathia
Broad nose
Long slender fingers
Developmental delay
Autistic spectrum disorder
A

DiGeorge syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

A patient shows these symptoms, what is the syndrome?
Saggy cheeks, widespaced teeth, full lips, stellate irides
Joint laxity
Developmental delay
“Cocktail party” speech & personality
Supravalvular aortic stenosis
Hypercalcaemia
Deletion knocks out Elastin gene on chr 7

A

Williams Syndrome

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Describe Amniocentesis

A

Usually between 14-18 weeks ofpregnancy
Risk of miscarriage
Can analyse amnioticfluid, & cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Describe Chorion Villus Sampling (CVS)

A

Samples contain cellular fetal material
Suitable for direct enzyme analysis & DNA extraction
CPM (confined placental mosaicism)
Good for T1 diagnosis of single gene & metabolic disorders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Describe Non-invasive prenatal testing (NIPT)

A

Cell-free fetal DNA in maternal circulation (>6wks)
Y chromosomal material
- PRESENT: male fetus
- ABSENT: female fetus
Quantification of specific chromosomal sequences, eg Tri 21
Indentification of paternal mutations, eg HD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

BRCA1 & BRCA2 breast/ovarian cancer:
What is the pattern of inheritance?
What kind of screening can be done?
What kind of surgery can be done to reduce risk?

A

Males and females can carry the gene

MRI, mammogram, ovarian screening

Mastectomy & bilateral saplingo-oophorectomy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

What are the main symptoms of Retinitis Pigmentosa

A

Primarily affects rod photoreceptors:
- night blindness, loss of peripheral vision, ultimately loss of central vision

Extremely heterogeneous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Describe the genetic heterogeneity in Cystic Fibrosis and how this influences patient outcome/treatment

A

One diseases - one gene - many mutations
Mutations in CFTR gene which encodes an ion channel - normal channel moves chloride ions fo outside of cell whereas mutant CFTR channel does not
Can be too few and/or dysfunctional channels

Genetic diagnosis can guide therapy:
- identify class of defect
Therefore can be treated with:
- correctors - increase quantity of protein produced
- potentiators - enhance remaining CFTR function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Outline the extensive genetic heterogeneity underlying Retinitis Pigmentosa

A

One disease - many genes - many mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

What are DNA markers

A

Regions of DNA that vary between individuals
Chromosomal location known
Allows you to see if the disease gene is close to or ‘linked’ to the DNA marker

Repeated sequences
<6 bp: Microsatellites /Short tandem repeats (STRs)
Minisatellites/Variable number tandem repeats (VNTRs)
Single nucleotide polymorphisms (SNPs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What is genetic heterogeneity

A

Genetic heterogeneity is a phenomenon in which a single phenotype or genetic disorder may be caused by any one of a multiple number of alleles from the same gene or mutations in several genes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

What is Pleiotropy

A

Single gene contributes to multiple phenotypic traits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What is the difference between Mendelian and multifactorial disease

A

Mendelian - one mutation on one gene

Multifactorial - involve other genes or factors such as environment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

Describe what is meant by fully penetrant conditions

A

Other genes and environmental factors have no apparent effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

What is meant by low-penetrance genes

A

They have a small influence, along with other genetic and environmental factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

What does llambda symbol represent in family studies and what does the subscript denote

A

Risk ratio

Subscript letter denotes the family relationship/member for whom the ratio was calculated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

In twin studies what do these terms mean

a) monozygotic
b) dizygotic
c) concordant
d) discordant

A

a) identical twins
b) non-identical twins
c) both twins are affected or unaffected
d) only one twin is affected

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

Define the differences between inherited and somatic cancer

A

Inherited then it must show that it has been passed on through the family - certain forms are inherited but not all

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

Define the key hallmarks of cancer

A
  • self-sufficiency in growth signals
  • insensitivity to antigrowth signals
  • tissue invasion and metastasis
  • limitless replicative potential
  • sustained angiogenesis
  • evading apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

Outline the most relevant molecular mechanisms in the development of cancer

A
  • translocation or transposition - gene moved to new locus, under new controls - give rise to producing a lot of copies of a particular gene
  • gene amplification - multiple copies of the gene
  • point mutation within a control element
  • point mutation within the gene - hyperactive or degradation-resistant protein
91
Q

List example roles of genetics in human congenital abnormalities

A

Down’s syndrome - chromosome abnormalities

Cystic fibrosis - single gene disorder

92
Q

Describe key differences and similarities between diagnostic, presymptomatic, carrier, and susceptibility genetic testing

A

Diagnostic:
Testing patient, following clinical findings to confirm genetic diagnosis

Presymptomatic:

  • Newborn screening: test newborn to identify immediate conditions that require immediate initiation of treatment to prevent death or disability
  • Prenatal testing: identify fetes with a genetic condition. Usually initiated on the basis of maternal factors or family history that indicate increased risk. However sometimes offered routinely

Carrier:
To identify an asymptomatic adult who is a carrier for autosomal-recessive or X-linked recessive conditions. Usually initiated on basis of family history

Genetic:
- Tests for adult onset genetic conditions: asymptomatic young adults to identify condition that will occur later in life

Susceptibility;
- Assessment of genetic risk for common complex diseases - identify an increased risk of future health problems eg heart disease or diabetes

93
Q

Compare options for population-based screening of ‘single gene’ and complex diseases

A

Single Gene:

  • Chromosomes: cytogenetic analysis - Down Syndrome
  • Specific mutation: testing known mutation in the family - cystic fibrosis
  • Specific gene

Complex Diseases:

  • Panel of genes: test multiple genes that might harbour the disease causing gene
  • Whole Genome: NGS of all 3 billion bases in human genome
94
Q

Define why population ancestry may be important

A

The frequency of genetic variation varies between populations of different ancestry

95
Q

Describe examples of current population genetic screening programmes and recognise basic parameters governing population genetic screening

A
  • Down’s, Edwards’ & Patau’s syndrome combined test
  • Sickle cell disease
  • Thalassaemia
  • Newborn and infant physical examination (NIPE)
  • tests for congenital heart disease
    developmental dysplasia of the hip
    congenital cataracts
    cryptorchidism (undescended testes)
  • Ultrasound
  • Newborn blood spot test

Considerations:

  • inform diagnosis/prognosis?
  • inform treatment?
  • is there support available?
  • reliable?
  • consent?
  • when do you tell them unexpected findings?
96
Q

How do transcription factors regulate gene expression

A

Molecular switches

DNA packaged in chromosome
Activator binds regulatory elements
Transcription factors and RNA polymerase recruited
Transcription activated

97
Q

How do microRNAs effect gene expression

A

Regulate the expression of many mRNAs by binding to sequences in the 3’ untranslated region of protein coding genes

98
Q

What is genetic imprinting

A

Determination of gene expression by parental origin

99
Q

How does DNA methylation work

A

Gene inactivation
Methylation (addition of CH3) occurs on cytosine of CpG’s (when cytosine lies next to guanine in the DNA sequence)
Forms 5-methyl cytosine
Is reversible
Can be inherited or changed with drugs/lifestyle

100
Q

Draw the main pedigree symbols for:
Male, female, sex undesignated, adopted, pregnancy, deceased, affected with trait, carrier for trait, carrier for x linked trait, mating, consanguineous mating, siblings, divorced or separated, miscarriage, dizygotic twins, monozygotic twins, no offspring, patient initiating genetic work up, two matings

A

See tutorial two

101
Q

What are the three main functions of the plasma membrane

A
  1. Receiving information
  2. Import and export of molecules
  3. Capacity for movement and expansion
102
Q

What does amphipathic mean in relation to the plasma membrane

A

Contains both hydrophilic and hydrophobic bits

103
Q

What will pure phospholipids form in water

A

Liposomes

104
Q

Which will dissolve in water - hydrophyllic or hydrophobic molecules

A

Hydrophyllic

105
Q

What does the fluidity of the plasma membrane depend on

A
  1. Which phospholipids are present
  2. The properties of hydrocarbon tails:
    - length: short chains - increases fluidity (18-20 carbon atoms is typical length)
    - number of double bonds - double bonds increase fluidity - decreasing packaging
106
Q

How does surfactant in lungs keep airways open

A

Alveoli in lungs requires surfactant

It decreases surface tension and allows bubbles to form in alveoli which keeps airways open

107
Q

What effect does cholesterol have on the plasma membrane

A

Stiffens up cell membranes
Prevents fluidity
Fills spaces between phospholipids left by their kinks from the unsaturated hydrocarbon tails - this decreases fluidity

108
Q

Why is membrane fluidity important

A
  • Allows membrane proteins to diffuse in the 2D-plane of the membrane
  • allows membrane lipids to move within the bilayer
  • allows membranes to fuse with each other and exchange contents
  • ensures equal distribution of cell contents between daughter cells when a cell divides
109
Q

What phospholipid is always on the inside layer of the plasma membrane

A

Phosphatidylinositol (PI)

110
Q

What do flip-flop enzymes do. Explain the 3 types

A

Move lipids across the bilayer

Flippases: outside in
Floppases: inside out
Scramblases: both directions

111
Q

What are glycoproteins and what is their function

A

Sugars attached to proteins

Protect cell from damage
Slimy surface
Involved in cell-cell communication
Give cells particular identity (eg can tell if liver cell, fat cell etc)

112
Q

What is the cell cortex

A

Mesh like structure
Protein framework
Supports and strengthens cell membrane

113
Q

Briefly describe passive and active transport

A

Passive: passage along concentration gradient - no energy needed
Active: against concentration gradient - requires energy - involves 2 types of membrane proteins: transporters and ion channels

114
Q

Name examples of local and long distance cell signalling

A

Local:

  • contact
  • paracrine
  • aurocrine
  • synaptic

Long distance:

  • endocrine
  • neuronal
115
Q

Describe paracrine signalling and give some examples of it

is it local or long distance

A

Local

Paracrine signaling: signaling in which the target cell is close to the signal
releasing cell, and the signal chemical is broken down too quickly to be carried
to other parts of the body.

Example of Paracrine Signalling:

Insulin-like growth factor (IGF-1) signalling in
Melanoma

Clotting agents in thrombus formation

Inflammatory mediators e.g. TNFa

116
Q

Describe neuronal/synaptic signalling and give an example

Is it local or long distance

A

Local

Synaptic signaling: from a nerve to a target cell (e.g. muscle)

Example: breathing: phrenic nerve (neutron) and diaphragm (muscle cells)

117
Q

Describe autocrine signalling and give some examples

Is it local or long distance

A

Local

Autocrine signaling: is a form of signaling in which a cell secretes a chemical
messenger that signals the same cell.

Examples of Autocrine Signaling:

Cancer cells

Interleukin-I (IL-1) in monocytes (immune)

IL-2 signaling in T-cells

118
Q

Give an example of endocrine cell signalling

A 
insulin hormone:
food eaten 
increased blood glucose
release of insulin form pancreas
insulin travels in the blood to stimulate glucose uptake into muscle liver and fat cells
119
Q

What is the basic model of signal transduction pathways

A 
extracellular signal molecule
receptor protein
intracellular signalling molecules
effector proteins
cell responses
120
Q

Describe the mechanism of G-protein coupled receptor signalling and the role of G proteins

A
  • GPCRs are proteins that span the membrane 7 times
  • examples: adrenaline, acetylcholine, dopamine, light, olfaction
  • active GPCRs trigger activation of G-proteins
  • G-proteins are made up of alpha and betagama
    subunits
  • inactive G-proteins contain GDP
    bound to the a-subunit
  • activation of G-proteins by GPCR
    swaps GDP for GTP
  • active G-protein can then activate
    its effector and transmit the signal
  • signal turned off by the hydrolysis
    of GTP –> GDP

G proteins operate as “switches” on cells
G-proteins activate enzymes that generate “second messengers” in the cell

121
Q

Identify how Receptor Tyrosine kinase signalling functions, and the role
of tyrosine phosphorylation

A
  • Enzyme coupled receptors
  • Receptors form dimers that span plasma membrane once
  • receptors arenezymes that phosphorylate tyrosine amino acids
  • RTKs control cell growth, cell division and other ‘slower’ cellular responses
  • on/off switch for RTKs depends on phosphorylation of tyrosine
122
Q

Explain how G protein signalling is altered in infectious disease such as cholera

A

Target of cholera toxin is G protein called Gs
Cl- secretion into the gut is controlled by Gs protein and cAMP
Cholera toxin prevents GTP breakdown, keeping Gs in the “on” conformation, triggering excessive Cl- excretion

Cholera toxin modifies the Gs protein via ADP ribosylation (adding a big sugar group)
This keeps Gs protein switched “on” by preventing breakdown of GTP
This causes overproduction of cAMP and excess Cl- is pumped out of the gut epithelial cells
This causes water and other salts to be pumped out, causing dehydration, loss of electrolytes etc and diarrhoea

123
Q

Describe how altered chloride ion channel signalling contributes to cystic fibrosis

A

Disease caused by a deletion in the gene for the cAMP-dependent chloride channel pump (CFTR) in airway epithelial cells
Epithelial cells cant pump Cl- out of the cells
This decreases water secretion from the cells
Causes increased viscosity of the mucus (thickening)
Patient more prone to bacterial infections because they don’t clear the mucus from their lungs

124
Q

In one sentence describe how incorrect cell signalling causes cholera

A

Cholera toxin causes over-activation of G-proteins

125
Q

In one sentence describe how incorrect cell signalling causes paralysis

A

Botulinum toxin - inhibition of synaptic signalling via blockage of ACh release

126
Q

In one sentence describe how incorrect cell signalling causes cystic fibrosis

A

Mutations in Cl- ion channel - defective Cl- transport in lung

127
Q

In one sentence describe how incorrect cell signalling causes Parkinson’s disease

A

Lack of dopamine signalling via its GPCR

128
Q

In one sentence describe how incorrect cell signalling causes Muckle Well’s syndrome

A

Excessive IL-1 receptor signalling

129
Q

In one sentence describe how incorrect cell signalling causes breast cancer

A

Over-activation of EGF receptor tyrosine kinase (RTK)

130
Q

What is a nucleation site

A

Centrosome near the nucleus has y-tubulin rings and each ring serves as the starting point (nucleation site) for growth of a microtubule
The minus end of each tubule is embedded in the centrosome and growth occurs from the plus end

131
Q

Describe dynamic instability of microtubules

A

Microtubules anchored in the centrosome can grow but also shrink independently of each other
Allows cells to undergo rapid remodelling
If the growing microtubule doesn’t attach to something it shrinks
If it attaches to something it forms a stable link with the centrosome
Allowing for a highly organised MT network and helps position organelles in a cell

132
Q

How is microtubule dynamic instability regulated

A

Dynamic instability is regulated by G-proteins
Tubulin are G-proteins
Tubulin GTP forms the growing microtubule
When GTP is hydrolysed to GDP the tubule detaches and the microtubule shrinks

GTP = on 
GDP = off
133
Q

How can the direction of microtubule growth create polarisation of a cell

A

Microtubules can be stabilised by binding to capping proteins at the plus ends of their filaments
Depending on the direction of growth this binding to capping proteins can lead to polarisation of a cell

134
Q

What is the function of Lysyl hydroxylase and prolyl hydroxylase

A

Lysyl - adds OH to some lysines

Prolyl - adds OH to some prolines

135
Q

How is collagen synthesised

A

It is produced as procollagen which has additional peptides on the end of the protein to prevent assembly into fibrils
Procollagen is secreted our of the cell
Cleavage of propeptides (done by procollagen proteinases)
Collagen fibres now in the extracellular matrix

136
Q

What is the cause of Alport Syndrome

A

Mutations in genes for type IV collagen

137
Q

Give an example of an enzyme that breaks down the cellular matrix

A

Matrix metalloproteinases

138
Q

How do cells attach to the extracellular matrix

A

Adaptor molecule called fibronectin is needed
Cells bind fibronectin via transmembrane receptors called integrins
The integrins attach to the actin cytoskeleton and thus give the cel its tensile strength

139
Q

What is the difference between a glycoprotein and a proteoglycan

A

Glycoprotein:
- proteins with covalently linked carbohydrate

Proteoglycan:

  • extracellular proteins linked to complex negatively charged carbohydrates (GAGs)
  • sugar is predominant
140
Q

Name 4 functions of GAGs in the ECM

A
  • space filling - resistance to compression
  • regulation of molecular transport through the ECM
  • bind and act as a reservoir for growth factors that signal to cells
  • regulate cell migration and movement through the ECM
141
Q

What is the basal lamina made up of

A

It is a specialised ECM

Mad up of type IV collagen and laminin

142
Q

What is the function of tight junctions and what are they made up of

A

Leak proof seal between cells

Made up of proteins called claudins and occludins (ZO-1)

143
Q

What is the function of adherens junction

A

Joins actin bundle in one cell to similar bundle in neighbouring cell

144
Q

What is the function of desmosomes

A

Joins the intermediate filaments in one cell to those in a neighbour

145
Q

What is the function of gap junctions

A

Forms channels that allow small water-soluble molecules, including ions, to pass from cell to cell

146
Q

What is the function of hemidesmosomes

A

Anchors intermediate filaments in a cell to the basal lamina

147
Q

What is entropy

A

The degree of randomness or disorder of a system - greater the disorder the greater the entropy

148
Q

How is enzyme performance described through the Michaelis & Menten equation

A

The rate of a reaction (V) increases as the substrate increases, until a maximum is reached (Vmax) and is the point where all substrate binding sites are occupied

The Michaelis constant (Km) is the substrate concentration where half the maximum binding occurs (1/2Vmax)

The larger the Km, the weaker the substrate is bound to the enzyme

149
Q

Give an example of a coupled reaction

A

Glucose ➡️ glucose-6-phosphate

Catalysed by hexokinase

150
Q

What is ATP

A

Adenosine-5’-triphosphate

Energy

A molecule which contains three phosphates helped together by high energy bonds
When the third phosphate is cleaved, leaving ADP, energy is released to drive anabolic reactions

151
Q

Briefly describe glycolysis
Does it require oxygen
Where does it occur

A

Glycolysis is the pathway where the energy from glucose is harvested to generate NADH and ATP
Anaerobic pathway - no oxygen required
Occurs in the cytoplasm

152
Q

Draw the flow chart for glycolysis

A

See lecture 21

Slide 16

153
Q

Draw the flow chart for the energy investment phase of glycolysis

A

Lecture 21

Slide 17

154
Q

What is the enzyme involved in step 3 of the energy investment phase of glycolysis

A

Phosphofructokinase

155
Q

Draw the flow chart for the cleavage phase of glycolysis

A

Lecture 21

Slide 19

156
Q

Draw the flow chart for the energy generation phase of glycolysis

A

Lecture 21

Slide 21

157
Q

What happens to the NADH of glycolysis

A

If oxygen is present the NADH is re-oxidised to NAD+ by the electron transport chain
However glycolysis is in the cytoplasm and the ETC is in the mitochondria - NADH cannot transverse the mitochondrial membrane
Therefore the hydrogens and electrons of each NADH are transferred to glycerol phosphate which can transport across the membrane
Here glycerate phosphate reacts with FAD to produce FADH2 and results in the formation of 2 ATPs per NADH

158
Q

What happens to pyruvate when oxygen supply is limited. Draw the equation and name the enzyme involved

A

It is reduced to lactate (lactic acid)

Lecture 21
Slide 29

Enzyme = lactate dehydrogenase

159
Q

What happens to pyruvate in conditions of adequate oxygen

A

It is transported from the cytoplasm to the mitochondria by a specific membrane transporter (pyruvate translocase)

It is then irreversible oxidatively decarboxylated to acetyl Co-enzymeA (CoA)

See lecture 21, slide 34 for equation

160
Q

How many molecules of ATP does one molecule of NADH produce

A

3

161
Q

How many molecules of ATP does one molecule of FADH2 produce

A

2

162
Q

What are the products of one turn of the kreb cycle

A

3 NADH
1 GTP
1 FADH2
2 CO2

(One molecule of glucose produces 2 molecules of pyruvate/acetyl CoA - so therefore these values are really doubled if you are talking about how many per glucose molecule)

163
Q 
How many ATPs are generated per glucose molecule in total?
How many from:
glucose to pyruvate
2 pyruvate to 2 acetyl-CoA
2 x Kreb cycle
A

36

6
6
24

164
Q

What happens in glycogenesis

A

Glucose is converted to glycogen

Glycogen is a glucose store

165
Q

What happens in gluconeogenesis

A

6 high energy phosphate bonds are used to synthesise glucose from pyruvate

It is the only source of glucose during prolonged fasting

It occurs in the liver/kidneys

166
Q

What is the difference between glucogenic and ketogenic amino acids

A

Glucogenic:
Are degraded to pyruvate or citric acid cycle intermediates
Can supply glucogenesis pathway

Ketogenic:
Degraded to acetyl CoA or acetoacetyl CoA
Can contribute to synthesis of fatty acids or ketone bodies

167
Q

Which amino acids are ketogenic, glucogenic and both

A

Ketogenic:
Leucine
Lysine

Both:
Isoleucine
Phenylalanine
Threonine
Tryptophan
Tyrosine

Glucogenic:
The rest

168
Q

Which metabolic abnormality gives rise to the serious disease phenylketonuria?
A - homocysteine cannot be converted into methionine
B - phenylalanine cannot be converted into tyrosine
C - phenylalanine cannot be converted into alanine
D - tyrosine cannot be converted into phenylalanine

A

B

169
Q

Where does the urea cycle occur

A

Mainly in the liver and to a lesser extent in the kindeys

170
Q

What can be a result of urea cycle disorders

A

Very high circulating ammonium levels - life threatening

171
Q

What is the cause of gout

Name some methods of treatment

A

Accumulation of uric acid or sodium urate in tissues
Caused by increased production or decreased excretion of uric acid

Alleviate joint pain and inflammation
Avoid alcohol
Avoid fructose rich drinks
Increase renal excretion of uric acid - probenecid
Inhibit xanthine oxidase - allopurinol
172
Q

What is the cause and symptoms of Lesch-Nyhan Syndrome

A

Rare inherited X chromosome-linked recessive disorder

Complete loss of of HGPRT activity - reduces purine salvage - increases uric acid production

173
Q

Describe how fatty acids are stored

A

Stored in the body as fat (triglyceride)

Predominantly in adipose tissue (in adipocytes)

174
Q

How many ATPs are produced from one acetyl CoA

A

12

175
Q

How many FADH2, NADH and acetyl CoAs are produced by shortening a fatty acid by 2 carbons

A

Shortening the fatty acid by 2 carbons yields:
1 FADH2
1 NADH
1 acetyl CoA

176
Q

Describe lipolysis and B oxidation

A

Hormone sensitive adipose tissue lipase (HSL) released when body needs to mobilise energy stores
This regulates the release of fatty acids from stored triglycerides in adipose tissue
These can enter B-oxidation to provide energy (this occurs in the mitochondria)

Before oxidation the fatty acid is activated to fatty acyl-CoA in the outer mitochondria membrane - requires 1 ATP

B-oxidation is a 4 step cyclic process - takes off two carbons each cycle
Each cycle releases 1 acetyl-CoA, 1 FADH2 and 1 NADH
FADH2 and NADH enter electron transport chain
Acetyl-CoA can enter TCA cycle and produce more NADH and FADH2 (3 NADH, 1 GTP and 1 FADH)

177
Q

Describe the condition of MCADD (medium chain acyl dehydrogenase deficiency)

A

Medium chain acyl CoA dehydrogenase deficiency is a fat oxidation disorder and is inherited in an autosomal recessive manner
Leads to a build up of medium-chain fats which can become toxic
Subjects must rely on glucose for energy
Life threatening

178
Q

Describe briefly ketogenesis

A

If excess acetyl-CoA then it is converted to acetoacetyl CoA
This is then converted to ketone bodies (acetoacetate, B-hydroxybutyrate, acetone)

Occurs in the liver mitochondria

Important during fasting

179
Q

What are ketone bodies

A

Water-soluble compounds that are produced as by-products when fatty acids are broken down for energy in the liver

180
Q

Briefly describe lipogenesis

A

The process by which acetyl-CoA is converted to fatty acids, and subsequently triglycerides

181
Q

Where does fatty acid synthesis take place

A

In the cytosol

182
Q

What enzyme catalyses the first step (activation) of fatty acid synthesis

A

Acetyl-CoA carboxylase

183
Q

Lipogenesis occurs in the cytoplasm and requires acetyl-CoA
But acetyl-CoA is generated in mitochondria and cannot cross the inner mitochondria membrane
How do we supply acetyl-CoA for lipogenesis?

A

Acetyl-CoA combines with oxaloacetate to produce citrate
Citrate is transported into cytoplasm via membrane transporter
Citrate then cleaved to form acetyl-CoA and oxaloacetate

184
Q

Describe briefly the 3 steps of lipogensesis

A
  1. Activation:
    - in cytoplasm
    - acetyl-CoA carboxylate to malonyl-CoA
    - catalysed by acetyl-CoA carboxylase
  2. Elongation
    - catalysed by fatty acid synthase complex
    - adds two carbons at a time from malonyl-CoA with the loss of carbon dioxide
    - repeats until 16 C are added - palmitic acid
    - mainly occurs in the endoplasmic reticulum by enzymes called fatty acid elongates
  3. Termination
    - needs nerdy
    - palmitic acid is a 16C saturated fatty acid - max length that can occur using this enzyme complex
    -
185
Q

How does HMG-CoA reductase maintain cholesterol homeostasis

A

High cholesterol:

  • decrease HMG-CoA reductase transcription
  • causes reduced cholesterol production

Low cholesterol:

  • increased HMG-CoA reductase transcription
  • increased cholesterol production
186
Q

How do statins work

A

Inhibit HMG-CoA reductase - reduce cholesterol biosynthesis
Liver cells then begin to draw cholesterol out of circulation to make up for lack of synthesis
Thus circulating levels of cholesterol in the blood will fall

187
Q

What is the enzyme involved in complex I of the electron transport chain and what does it do

A

NADH-coenzyme Q reductase

Transfers electrons from NADH to Coenzyme Q

188
Q

What enzyme is involved in complex III of the ETC and what does it do

A

Coenzyme Q reductase

Transfers electrons from reduced CoQ to cytochrome c

189
Q

What is the enzyme involved in complex IV of the ECT and what does it do

A

Cytochrome c oxidase

Transfers electrons from cytochrome c to O2

190
Q

What is the enzyme involved in complex V of the ECT and what does it do

A

ATP synthase

Protons flow through this enzyme which uses energy to generate ATP

191
Q

What enzyme is involved in complex II of the ECT and what does it do

A

Succinate-coenzyme Q reductase

Transfers electrons from FADH2 to CoQ

192
Q

Where does oxidative phosphorylation occur

A

In the inner mitochondrial membrane

193
Q

What is a reactive oxygen species (ROS)

A

Any free radical involving oxygen

194
Q

What is meant by oxidative stress

A

General term used to describe the level of oxidative damage in a cell, tissue or organ caused by ROS

Reflects the balance between exposure to ROS and removal of them from the body

ROS can come from oxidative phosphorylation or also environmental ROS (eg smoke and pollutants)

195
Q

How do cells limit the damage caused by reactive oxygen species

A

Contain two antioxidant systems:
1. Antioxidant enzymes
2. Antioxidant vitamins
They neutralise ROS, limiting damage

196
Q

Name an enzyme involved in the enzymatic defence against oxidative stress

A

Superoxide dismutase

197
Q

What might the symptoms be for acute presentation of an inherited metabolic disease

A 
vomiting
lethargy
poor feeding
siezures
hypoglycaemia
metabolic acidosis
198
Q

What might be symptoms for chronic presentation of an inherited metabolic disease

A 
failure to thrive
organomegaly
seizures 
developmental delay
eye changes
199
Q

Name 3 foods which are restricted in a diet for PKU?

A

Meat
Fish
Nuts
Dairy

200
Q

What is the mode of inheritance for PKU?

A

Autosomal recessive

201
Q

List 3 consequences of untreated PKU?

A 
Fair skin and hair
Intellectual impairment
Epilepsy
Movement disorder
Autistic behaviour
Eczema
202
Q

What is the cause of PKU

A

genetic deficiency of Phenylalanine Hydroxylase

Phenylalanine and phenylpyruvate accumulate in blood and urine

203
Q

What is the cause of medium chain acyl dehydrogenase deficiency (MCADD)

A

People with this condition cannot break down fatty acids properly, because they lack one of the enzymes needed (Acyl CoA dehydrogenase)

This leads to a build-up of medium chain fats which can become toxic. They also cannot break down fatty acids for energy so rely on glucose

204
Q

Name 3 things involved in management of MCADD

A
  • avoid prolonged fasting
  • carbohydrates before bed
  • breakfast on time
  • advice regarding alcohol intake
  • have an emergency plan in place
205
Q

What causes urea cycle disorders/defects

A

Deficiency of one of the enzymes involved in the urea cycle

Urea cycle removes nitrogen from the blood and converts it to urea which can be excreted via urine

in urea cycle disorders the nitrogen accumulates in the form of ammonium which is a highly toxic substance and it cannot be removed from the body

206
Q

What kind of inheritance is OTC (ornithine transcarbamoylase) deficiency

A

X linked recessive

207
Q

How would you be able to diagnose a urea disorder (what are the signs)

A
  • v high ammonia levels ***
  • often mild alkalosis
  • plasma amino acids - may be high glutamine, low arginine
  • urine - orotic acid present
208
Q

When should you suspect familial hypercholesterolaemia (FH)

A

when the total cholesterol is > 7.5 mmol/L
or
personal or familial history of premature coronary heart disease

209
Q

Describe dysbetalipoproteinaemia - clinical features, diagnosis and treatment.

A

Clinical features:

  • autosomal recessive inheritance
  • needs a trigger, eg: obesity, diabetes, hypothyroidism or low oestrogen states in women
  • Markedly raised cholesterol and triglycerides
  • cutaneous lipid deposition
  • premature cardiovascular disease
Treatment:
- Lowering of LDL-cholesterol is the main aim
- Occasionally lowering of triglycerides is necessary
- Lifestyle changes can help:
Diet
Weight loss
Exercise
- Drugs are often required
210
Q

How do statins work

A
  • HMG CoA reductase inhibitors
  • causes decrease cellular cholesterol conc
  • this activates sterol regulatory element binding protein (SREBP) - up-regulates the gene encoding for LDL-receptor
  • increased LDL-receptor expression increases uptake of plasma LDL thus decreasing plasma LDL concentration
211
Q

How do fibrates work

A
  • activate nuclear transcription factor PPARa
  • modulation of target genes increases activity of lipoprotein lip and decrease synthesis of apo C-111
  • this decreases VLDL and triglycerides
212
Q

How does the drug Ezetimibe work

A

Neimann-pick C1 receptor inhibitor - inhibits gut cholesterol absorption

213
Q

How do PCSK9-inhibitors work

A

Monoclonal antibodies against pro protein converts subtilising-like/kexin-9
fortnightly or monthly subcutaneous injection

214
Q

Describe ketoacidosis

A

when large amounts of the ketone bodies acetoacetate and b-hydroxybutyrate are released from liver, the blood pH drops because they are acids

215
Q

In the absence of glucose, ketone bodies can be used as an energy source, with the exception of the following?

a) Adipocytes

b) Brain
c) Erythrocytes
d) Muscle
e) Lungs

A

c - erythrocytes

216
Q

The only source of glucose during prolonged fasting is:

Gluconeogenesis

Glycolysis

Glycogenolysis

Glycogenesis

Electron transport chain

A

gluconeogenesis

217
Q

How does diabetes effect the hormone regulation of metabolism. How is it diagnosed and treated

A
  • In diabetes, there is overproduction and underutilisation of glucose
  • There is an overproduction of fatty acids from adipose tissue – the liver turns these into ketone bodies and lipoproteins (VLDL)
  • Dentists occasionally may diagnose diabetes by the characteristic acetone smell on the breath (ketoacidosis)
  • Complete absence of insulin (untreated Type 1 diabetes) can lead to diabetic ketoacidosis and coma
  • Treatment is by insulin injection, fluid replacement and correcting blood pH
218
Q

What is the kinetochore

A

Specialised complex of proteins where spindle MT attach to chromosomes

219
Q

Name the three types of microtubules

A

astral microtubules
kinetochore microtubules
inter polar microtubules

220
Q

What enzyme regulates the cell cycle

A

Cyclin dependent kinases (CDKs)

221
Q

Briefly describe the cell cycle and its four phases

A

4 phases
G1:
Cells begin to gown

S:
Replicate

G2
Prepare for cell division

M
Cell division and cytokinesis

222
Q

What is replicative senescence

A

When cells go into a state where they cannot divide ever again

223
Q

What is the difference between necrosis and apoptosis

A

Apoptosis – programmed cell death – dies in coordinated way – no leakage

Necrosis – cell starts to die – part of this dying process its contents leak out – body reacts by initiating immune response – inflammation

224
Q

What is the difference between extrinsic and intrinsic apoptosis

A

Extrinsic pathway:

  • Activated by cell surface receptors
  • Death receptors
  • Activated by ligands binding to the receptors

Intrinsic pathway:

  • Activated by events within cells
  • Depends on mitochondria
  • Release of cytochrome c which can work with other proteins to activate caspases

Principles Of Disease And Treatment (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions